Medchemexpress/MSI-1436(Synonyms: Trodusquemine; Aminosterol-1436)/HY-12219/1mg

MSI-1436isaselective,non-competitiveinhibitoroftheenzymeproteintyrosinephosphatase1B(PTB-1B),withIC₅₀ofappr1μM,200-foldpreferenceoverTC-PTP(IC₅₀=224μM).

IC50:1μM(PTB-1B),224μM(TC-PTP)^[1]

InHepG2,MSI-1436(10µM,30min)alonehasnoeffectonphosphorylationofIRβ,butinconjunctionwith100nMinsulin,increasesp-IRβ18-foldoveruntreatedcellsandbyapproximatelythreefoldovercellstreatedwithinsulinalone.MSI-1436"sinhibitionofTCPTPisapproximatelytwologslessthantheeffectonPTP1Bactivity,witharesultingIC₅₀valueof224µM^[1].MSI-1436leadstoenhancedtyrosinephosphorylationofmGluR5inF11neuroblastomacells^[2].MSI-1436(0.1-100µM)blocksPTP1Bactivity,hasinsulin-mimeticeffectsinculturedneuronalcells^[3].

MSI-1436(10mg/kg,i.p.)causesobesity-dependentbodyweight,reducestotalbodyfatcontentandADIpocytesizeandlipidcontentofwhiteadiposetissueofmice.MSI-1436treatmentsignificantlyreducesplasmainsulinlevels.MSI-1436(10mg/kg,IP)increasesphosphorylationofSTAT-32.7-foldand,inconjunctionwith100U/kginsulin,p-IRβincreasesthreefoldoverinsulinalone-treatedrats^[1].MSI-1436attenuatesthedecreaseinlevelsofeCBsintheamygdalaofrestraintstress-treatedmiceanddecreasesstress-inducedanxiety^[2].MSI-1436(5mg/kg,i.p.)hasananti-diabeticeffectondiabeticmice,andissufficienttosuppressfoodintakeandcauseweightlossinCD1mice^[3].

• [1].LantzKA,etal.InhibitionofPTP1Bbytrodusquemine(MSI-1436)causesfat-specificweightlossindiet-inducedobesemice.Obesity(SilverSpring).2010Aug;18(8):1516-1523.

  [2].KrishnanN,etal.AnxiousmomentsfortheproteintyrosinephosphatasePTP1B.TrendsNeurosci.2015Aug;38(8):462-5.

  [3].QinZ,etal.FunctionalpropertiesofClaramine:anovelPTP1Binhibitorandinsulin-mimeticcompound.BiochemBiophysResCommun.2015Feb27;458(1):21-7.

MSI-1436isformulatedinsalineforbothmiceandratadministration.

Mice
MaleAKR/JmicearerandomLyplacedonadlibitum10,45,or60%fatkcaldiets.After-14weeks,micearerandomlyassignedtothreetreatmentgroups(n=5-8mice/group);MSI-1436(initialdoseof10mg/kgwiththreesubsequentweeklydosesof5mg/kg,intraperitoneally),vehicle(saline,10mL/kg,weekly4×),orpair-fed(PF).PFanimalsareinjectedwithsaline(weekly4×)andallottedtheamountoffoodconsumeddailybyMSI-1436-treatedanimals.Onday23,miceareanesthetizedandeuthanizedforbloodandtissuecollection,respectively.Plasmaisobtainedfollowingcentrifugationofblood14,000rpmfor10minat4°C.
Rat
Nine-week-oldmaleSprague-Dawleyrats(225-260g)withadlibitumaccesstonormalrodentchowaredosedintraperitoneallywithMSI-1436(10mg/kg,IP)orsaline.Afteranovernightfast,theratsaredosedintraperitoneallywithsalineor100U/kgofinsulin.At30minafterdose,animalsarekilled,andhypothalamiareharvestedandhomogenizedin1mLoftissueextractionreagentplusphosphataseandproteaseinhibitors.Samplesarecentrifuged(14,000rpmfor10minat4°C),andtheproteincontentofthesupernatantsarequantitatedviaBCAkit.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.

• [1].LantzKA,etal.InhibitionofPTP1Bbytrodusquemine(MSI-1436)causesfat-specificweightlossindiet-inducedobesemice.Obesity(SilverSpring).2010Aug;18(8):1516-1523.

  [2].KrishnanN,etal.AnxiousmomentsfortheproteintyrosinephosphatasePTP1B.TrendsNeurosci.2015Aug;38(8):462-5.

  [3].QinZ,etal.FunctionalpropertiesofClaramine:anovelPTP1Binhibitorandinsulin-mimeticcompound.BiochemBiophysResCommun.2015Feb27;458(1):21-7.

685.06

C₃₇H₇₂N₄O₅S

186139-09-3

RoomtemperatureincontinentalUS;mayvaryelsewhere

10mMinDMSO

*"<1 mg/ml"="" means="" slightly="" soluble="" or="" insoluble.="" "≥"="" means="" soluble,="" but="" saturation="">